Fig. 7: Schematic of eosinophil-mediated Siglec-Fhi neutrophil induction in asthmatic lungs.

(Top) In wild-type mice, GPR43 restrains eosinophil activation and the production of neutrophil chemoattractants, resulting in limited neutrophil recruitment and minimizing the generation of Siglec-Fhi neutrophils. (Bottom) In eosinophil-specific GPR43-deficient mice, infiltrating neutrophils are exposed to elevated levels of IL-4 and upregulate PECAM-1 expression. GPR43-deficient eosinophils are hyperactivated, produce more neutrophil chemoattractants, and express higher levels of PECAM-1 compared with wild-type eosinophils. These changes lead to enhanced neutrophil recruitment and stronger eosinophil-neutrophil interactions, promoting the induction of Siglec-Fhi neutrophils via eosinophil-derived IL-4 and GM-CSF. Siglec-Fhi neutrophils, in turn, promote Th17 cell differentiation. Created in BioRender. Yu, J. (2025) https://BioRender.com/d0uv25k.